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  • 1
    Electronic Resource
    Electronic Resource
    On the shock enhancement of confined supersonic mixing flows (1991)
    New York, NY : American Institute of Physics (AIP)
    Physics of Fluids 3 (1991), S. 3046-3062 
    Details
    ISSN: 1089-7666
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Direct numerical simulations using high-resolution total variation diminishing (TVD) scheme are performed for studying the shock enhancement of two-dimensional confined (spatially growing) supersonic mixing flows. Several specially designed mixing enhancement schemes are examined with emphasis placed on the study of the fundamental aspects involved in the shock-induced mixing enhancement process. The merits associated with these mixing enhancement schemes are evaluated based on a cost/effectiveness criterion, in which the cost paid for the total pressure loss encountered and the improvement in mixing gained are considered together. The results suggest that mixing enhancement using shock waves can only be effective if the stimulation is spatially persistent, and begins from the very upstream. Being motivated by this observation, an idea of using wavy-wall configuration to generate the desirable periodic shock stimulation is proposed and investigated. The computed results show that, by an appropriate manipulation of the parameters including wall wavelength, relative phase shift between the top and bottom walls, as well as the amplitude of the waviness, considerable improvement in mixing efficiency can be achieved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.857849
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  • 2
    Electronic Resource
    Electronic Resource
    Numerical investigation on the structure of a confined supersonic mixing layer (1991)
    New York, NY : American Institute of Physics (AIP)
    Physics of Fluids 3 (1991), S. 3063-3079 
    Details
    ISSN: 1089-7666
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Direct numerical simulations using the high-resolution TVD scheme are performed for the study of two-dimensional confined spatially growing supersonic mixing layers. Numerical simulations, being forced by the linear instability wall modes, are justified by comparing the calculated results with both theoretical and experimental data. The numerically visualized downstream compression/expansion wave system explains the so-called "strange waves'' observed in experiments and are found to be responsible for the rapid growth of the mixing layer in that region. The existence of shock waves would lead to mixing enhancement by accelerating the process of extracting turbulent kinetic energy from the mean stream. However, the phenomenon of shock-induced mixing improvement is found quite local around the shock impingement area, and often is followed by a saturation in turbulent energy absorption which impedes the further growth of the shear layer in the immediate downstream region. For the present cases considered, the subharmonic instability modes are not dominant, and the baroclinic-torque effect is comparatively less important for the vorticity development. These observations suggest that compressibility effects may behave in a considerably different manner as the underlying instability mechanism changes from the subsonic Kelvin–Helmholtz type to the present supersonic wall instability type.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.857850
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  • 3
    Electronic Resource
    Electronic Resource
    The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-β production (2007)
    [s.l.] : Nature Publishing Group
    Nature 446 (2007), S. 342-342 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Nature 440, 528–534 (2006) During editing to meet Nature’s limits on length, we removed a reference to an earlier paper1 reporting that the prolyl isomerase Pin1 promotes production of Alzheimer’s ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nature05606
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  • 4
    Electronic Resource
    Electronic Resource
    d-myo-Inositol 1,4,5-trisphosphate analogues as useful tools in biochemical studies of intracellular calcium mobilization
    Amsterdam : Elsevier
    Bioorganic and Medicinal Chemistry 2 (1994), S. 7-13 
    Details
    ISSN: 0968-0896
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/S0968-0896(00)82196-3
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  • 5
    Electronic Resource
    Electronic Resource
    The midgut chymotrypsins of shrimps (Penaeus monodon, Penaeus japonicus and Penaeus penicillatus)
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular 1080 (1991), S. 59-67 
    Details
    ISSN: 0167-4838
    Keywords: (Shrimp) ; Amino acid sequence ; Chymotrypsin ; Collagenolysis ; Kinetic salt effect ; Kinetic specificity
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0167-4838(91)90112-D
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  • 6
    Electronic Resource
    Electronic Resource
    Phosphorylation-dependent prolyl isomerization: a novel signaling regulatory mechanism (1999)
    Springer
    Cellular and molecular life sciences 56 (1999), S. 788-806 
    Details
    ISSN: 1420-9071
    Keywords: Key words. Alzheimer’s disease; mitotic regulation; Pin1; peptidyl-prolyl isomerase; prolyl isomerization; protein phosphorylation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Protein phosphorylation on serine or threonine residues preceding proline (Ser/Thr-Pro) plays an essential role for regulating various cellular processes, including cell cycle progression. Although phosphorylation has been proposed to regulate the function of a protein by inducing conformational changes, much less is known about what phosphate additions actually do and how the functions of phosphoproteins are coordinated. Proline is important for determining protein structure because it exists in cis or trans conformation and can put kinks into a polypeptide chain. We have shown that phosphorylation on Ser/Thr-Pro motifs reduces the cis/trans isomerization rate of Ser/Thr-Pro bonds. At the same time, proteins containing phosphorylated Ser/Thr-Pro motifs are substrates for the prolyl isomerase Pin1. The WW domain of Pin1 acts as a phosphoserine/threonine-binding module binding a defined subset of mitosis-specific phosphoproteins, such as Cdc25 and tau. These interactions target the enzymatic activity of Pin1 close to its substrates. In contrast to other prolyl isomerases (peptidyl-prolyl isomerases, PPIases), Pin1 has an extremely high degree of substrate specificity, specifically isomerizing phosphorylated Ser/Thr-Pro bonds. Therefore, Pin1 binds and regulates the function of a defined subset of phosphoproteins. Furthermore, inhibiting Pin1 function is lethal for dividing cells. Interestingly, Pin1, which can restore the biological function of phosphorylated tau, is sequestered in the neurofibrillary tangles in Alzheimer’s brains. Thus, we have proposed a novel signaling regulatory mechanism, where protein phosphorylation creates binding sites for Pin1, which can then latch on to and isomerize the phosphorylated Ser/Thr-Pro peptide bond. In turn, this may change the shape of the protein, regulating its activity, dephosphorylation, degradation or location in the cell. This new post-phosphorylation regulatory mechanism appears to play an important role in normal cell function, such as mitotic progression, and in the pathogenesis of some human pathologies, such as Alzheimer’s disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000180050026
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  • 7
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    CTMP Promotes Akt Activation and Tumorigenesis (2013)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2013-10-16
    Description: Akt activation has been implicated broadly in tumorigenesis, but the basis for its dysregulation in cancer cells is incompletely understood. In this study, we sought to clarify a regulatory role for the Akt-binding carboxy-terminal modulator protein (CTMP), which has been controversial. In evaluating CTMP expression in paired normal–tumor specimens of 198 patients with breast cancer, we found that CTMP was upregulated in breast tumors, where it was associated with poor patient survival. Notably, CTMP expression also correlated positively with Akt phosphorylation in breast cancer clinical specimens and cell lines. Furthermore, ectopic expression of CTMP promoted cell proliferation and enhanced the tumorigenic properties of estrogen-dependent breast cancer cells. This effect was correlated with increased sensitivity to insulin-induced Akt phosphorylation, which is mediated primarily by the phosphoinositide 3-kinase–Akt pathway. In contrast, short hairpin RNA-mediated silencing of endogenous CTMP decreased the proliferation of estrogen-dependent or estrogen-independent breast cancer cells. Mechanistic investigations defined the N-terminal domain of CTMP at amino acids 1 to 64 as responsible for Akt binding. Taken together, our results firmly corroborate the concept that CTMP promotes Akt phosphorylation and functions as an oncogenic molecule in breast cancer. Cancer Res; 73(20); 6194–205. ©2013 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 8
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    Loss of RUNX3 increases osteopontin expression and promotes cell migration in gastric cancer (2013)
    Oxford University Press
    Details
    Publication Date: 2013-10-30
    Description: Loss of RUNX3 expression is frequently observed in gastric cancer and is highly associated with lymph node metastasis and poor prognosis. However, the underlying molecular mechanisms of gastric cancer remain unknown. In this study, we found that the protein levels of RUNX3 and osteopontin (OPN) are inversely correlated in gastric cancer clinical specimens and cell lines. Furthermore, similar inverse trends between RUNX3 and OPN messenger RNA (mRNA) expression were demonstrated in six out of seven normal-tumor-paired gastric cancer clinical specimens. In addition, low RUNX3 and high OPN expression were associated with poor prognosis in gastric cancer patients. Ectopic expression of green fluorescent protein-RUNX3 reduced OPN protein and mRNA expression in the AGS and SCM-1 gastric cancer cell lines. In contrast, knockdown of RUNX3 in GES-1, a normal gastric epithelial cell line, increased OPN expression. Although three RUNX3-binding sequences have been identified in the OPN promoter region, direct binding of RUNX3 to the specific binding site, –142 to –137bp, was demonstrated by chromatin immunoprecipitation assay. The binding of RUNX3 to the OPN promoter significantly decreased OPN promoter activity. The knockdown of OPN or overexpression of RUNX3 inhibited cell migration in AGS and SCM-1 cells; however, the coexpression of RUNX3 and OPN reversed the RUNX3-reduced migration ability in AGS and SCM-1 cells. In contrast, the knockdown of both RUNX3 and OPN inhibited RUNX3-knockdown-induced migration of GES-1 cells. Together, our data demonstrated that RUNX3 is a transcriptional repressor of OPN and that loss of RUNX3 upregulates OPN, which promotes migration in gastric cancer cells.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
    Published by Oxford University Press
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  • 9
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    MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway (2013)
    Oxford University Press
    Details
    Publication Date: 2013-02-27
    Description: Prostate cancer (PCa) is a leading cause of mortality and morbidity in men worldwide, and emerging evidence suggests that the CD44 high prostate tumor-initiating cells (TICs) are associated with its poor prognosis. Although microRNAs are frequently dysregulated in human cancers, the influence of microRNAs on PCa malignancy and whether targeting TIC-associated microRNAs inhibit PCa progression remain unclear. In this study, we found that miR-320 is significantly downregulated in PCa. Overexpression of miR-320 in PCa cells decreases PCa tumorigenesis in vitro and in vivo . Global gene expression profiling of miR-320-overexpressing PCa cells reveals that downstream target genes of Wnt/β-catenin pathway and cancer stem cell markers are significantly decreased. MicroRNA-320 inhibits β-catenin expression by targeting the 3'-untranslated region of β-catenin mRNA. The reduction of miR-320 associated with increased β-catenin was also found in CD44 high subpopulation of prostate cancer cells and clinical PCa specimens. Interestingly, knockdown of miR-320 significantly increases the cancer stem-like properties, such as tumorsphere formation, chemoresistance and tumorigenic abilities, although enriching the population of stem-like TICs among PCa cells. Furthermore, increased miR-320 expression in prostate stem-like TICs significantly suppresses stem cell-like properties of PCa cells. These results support that miR-320 is a key negative regulator in prostate TICs, and suggest developing miR-320 as a novel therapeutic agent may offer benefits for PCa treatment.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
    Published by Oxford University Press
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  • 10
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    Uptake of Pneumococcal Polysaccharide Vaccination Among Working-age Adults With Underlying Medical Conditions, United States, 2009 (2012)
    Oxford University Press
    Details
    Publication Date: 2012-04-14
    Description: Since 1997, the Advisory Committee on Immunization Practices has recommended the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for nonelderly adults with certain medical conditions. In 2008, the Committee added asthma and cigarette smoking to the list of indications for PPSV23 vaccination. Using data from the 2009 National Health Interview Survey, the authors assessed PPSV23 uptake in people with established and new indications. To identify factors independently associated with receiving PPSV23, they used multivariable logistic regression and predictive marginal analyses. In 2009, a total of 35.2 million adults 18–64 years of age (18.6%) had established PPSV23 indications; adding asthma and smoking to the list of indications increased the high-risk population to 71.6 million people (37.9%). Overall, 26.1% of people with established indications for PPSV23 and 17.4% of people with any indication (those previously established, as well as asthma and smoking) had received the vaccine; overall coverage among persons 50–64 years of age was significantly higher than that among persons 18–49 years of age (34.6% vs. 16.7%; P 〈 0.001) and for all specific indications except cancer. For persons who had asthma or who smoked but had no other indications, rates of coverage were 12.3% and 8.5%, respectively. In persons who had established indications, being older, white, and unemployed and having more physician visits, a prior hospitalization, a regular physician, and health insurance were independently associated with PPSV23 receipt. PPSV23 uptake varies substantially by age and indication but remains low overall, with approximately 59 million unvaccinated high-risk working-age adults. Effective strategies to increase pneumococcal vaccination coverage among at-risk groups are needed.
    Print ISSN: 0002-9262
    Electronic ISSN: 1476-6256
    Topics: Medicine
    Published by Oxford University Press
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